The Impact of Thymoquinone on p۵۳ Gene Expression in Breast Cancer, Insights and Therapeutic Potential; A Systematic review

Abstract Introduction: Breast cancer is a leading cause of cancer-related mortality in women globally, especially in developing countries. The use of herbal medicine therapies has gained significant attention in contemporary times. Thymoquinone (TQ) is the active compound of Nigella sativa. It has antioxidant and anticancer properties and can be used to treat breast cancer through various molecular pathways. The p۵۳ gene is a critical tumor suppressor, therefore targeting its function can be a potential therapeutic strategy. Given the outdated information and lack of clear evidence regarding the impact of TQ on p۵۳ gene expression in breast cancer and its therapeutic mechanisms, we found it crucial to compile and analyse this issue. This systematic review aimed to comprehensively investigate the effects of TQ on p۵۳ gene expression and its potential therapeutic effect in MCF-۷ breast cancer cell line. Method: We developed a systematic search strategy for each database including PubMed, Embase, and Scopus, following the PICO framework without any time limitation. We used EndNote۲۱ for the deduplication of yielded citations and subsequently uploaded results to Rayyan.ai for title, abstract, and full-text screening. We included studies that investigated the effect of TQ on p۵۳ gene expression in MCF-۷ breast cancer cell line and its underlying mechanisms. Each reviewer independently screened their assigned articles using a double-blind method. In instances of disagreement, a third reviewer was engaged to resolve conflicts. The PRISMA flow diagram was provided for a clear overview of the article selection process, and the reasons for excluding the remaining articles. Data extraction was conducted using specific tables, with the double-blind paired approach. Results: Our search yielded overall ۴۶۵۴ studies. After screening the full-texts of ۳۱ studies, ۸ articles finally met the inclusion criteria and were selected for data synthesis. In the studies usage of flow cytometry indicated that TQ, induces apoptosis in MCF-۷ cells at various time points, with the apoptotic effect increasing over time. All results suggested that the induction of apoptosis in breast cancer cells by TQ needs the activation of p۵۳ gene expression. PCR was conducted to assess this phenomenon and showed that P۵۳ gene expression was significantly upregulated over time, particularly after ۷۲ hours of treatment, leading to a notable increase in p۵۳ protein levels in the cell line. One study suggested that TQ reduces Akt expression, leading to decreased MDM۲ activation, which subsequently promotes p۵۳-mediated apoptosis in breast cancer cell line. Conclusion: The induction of apoptosis in MCF-۷ cell line by TQ through the upregulation of the p۵۳ gene, suggests a potential therapeutic role for this natural compound in breast cancer. This discovery warrants further investigation into TQ's mechanisms of action and its potential synergistic effects with existing cancer therapies. The exploration of natural compounds like TQ holds promise for developing novel and effective strategies to manage breast cancer.

کلیدواژه ها:

Breast cancer ، Thymoquinone ، p۵۳ ، Nigella sativa